Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA.
Arch Oral Biol. 2009 Mar;54(3):279-86. doi: 10.1016/j.archoralbio.2008.11.003. Epub 2008 Dec 19.
MMP13 is enriched in mature chondrocytes and considered a prime cause of ECM degradation in the osteoarthritic articular cartilage in temporomandibular joints. We asked whether surviving stress to the endoplasmic reticulum (ER) would upregulate transcription of MMP13, and if so, whether a cross-talk would exist between surviving ER stress and p38 MAPK pathways. Using C28/I2 chondrocyte cell line, ER stress was induced by thapsigargin and tunicamycin and upregulation of phosphorylated eIF2alpha and ATF4 protein was observed. Both thapsigargin and tunicamycin elevated the mRNA level of MMP13 and phosphorylation of p38 MAPK. Thapsigargin-induced MMP13 mRNA upregulation was significantly suppressed by SB203580, while its upregulation by tunicamycin was completely attenuated by SB203580. Those results support that homeostasis of chondrocytes is affected by the surviving ER stress through p38 MAPK pathways, suggesting a potential role of ER stress in joint diseases such as osteoarthritis.
MMP13 在成熟的软骨细胞中富集，被认为是颞下颌关节骨关节炎关节软骨中细胞外基质降解的主要原因。我们想知道内质网（ER）存活压力是否会上调 MMP13 的转录，如果是这样，那么 ER 存活压力和 p38 MAPK 途径之间是否存在串扰。使用 C28/I2 软骨细胞系，用他普西龙和衣霉素诱导 ER 应激，观察到磷酸化 eIF2alpha 和 ATF4 蛋白的上调。他普西龙和衣霉素均能上调 MMP13 的 mRNA 水平，并磷酸化 p38 MAPK。SB203580 显著抑制他普西龙诱导的 MMP13 mRNA 上调，而 SB203580 完全抑制衣霉素诱导的 MMP13 mRNA 上调。这些结果表明，内质网应激通过 p38 MAPK 途径影响软骨细胞的稳态，提示内质网应激在骨关节炎等关节疾病中的潜在作用。
